Conclusions

• The craniofacial patterning transcription factor FOXC1 was found to be widely expressed in a large cohort of meningiomas.
• FOXC1 expression is inversely correlated with WHO tumor grade.
• FOXC1low meningiomas are significantly more likely to harbor NF2 mutations than FOXC1hi meningiomas.
• FOXC1 expression levels are correlated with high expression of other meningeal identify genes suggesting low levels of FOXC1 may represent dedifferentiation to a more immature state.
• Multi-omic analysis reveals a significant relationship between FOXC1 transcript levels and key markers of the immune environment including PDL1 transcript expression.
• Functional studies are warranted to determine whether FOXC1 is necessary for meningioma growth, whether FOXC1 plays a direct immunomodulatory role in meningiomas, and whether the lower FOXC1 expression levels in high grade tumors represent a more embryonic phenotype.